A Safety and Efficacy Study of CC-122 in Combination With Nivolumab in Subjects With Unresectable Hepatocellular Carcinoma (HCC)
A Phase 1/2, MultiCenter, Open-label, Dose Finding Study to Assess the Safety, Tolerability and Preliminary Efficacy of CC-122 in Combination With Nivolumab in Subjects With Unresectable Hepatocellullar Carcinoma (HCC) Following First Line Treatment Failure
調査の概要
詳細な説明
Study population included subjects who had progressed after or were intolerant to no more than 2 previous systemic therapies for unresectable HCC, or are naïve to systemic therapy.
The dose escalation part of the study was designed to explore three dose levels of CC-122 to identify the recommended phase 2 dose (RP2D) to be used in the expansion phase. Approximately 20 subjects were to be enrolled in the dose escalation part of the study. Subjects could be treated for up to 2 years, or until progression of disease, unacceptable toxicity, subject/physician decision, withdrawal of consent, death. Safety follow up until 28 days after CC122 treatment and 90 days after nivolumab treatment. RECIST 1.1 criteria was used to determine response. Survival follow up until death, withdrawal of consent, or the study closes. Subjects were permitted to continue treatment beyond progression (TBP) if they continue to meet protocol criteria, had stable performance status, had clinical benefit, other treatment options were discussed. A separate ICF was signed to continue TBP.
During the dose escalation phase, CC-122 was administered orally 5 consecutive days out of 7 (5 days on/2 days off weekly) on Days 1 to 5, 8 to 12, 15 to 19 and 22 to 26 of each 28-day cycle. Once the RP2D for dosing of CC-122 in combination with nivolumab was defined, expansion (Phase 2) would start. A modified 3+3 dose escalation design was used to identify the initial toxicity of the combination. Up to six subjects were concurrently enrolled into a dose level. Decisions as to which dose level to enroll a new subject were based on the number of subjects enrolled and evaluable, the number of subjects experiencing DLTs, and the number of subjects enrolled but who are not yet evaluable for toxicity in the current cohort at the time of new subject entry. A Safety Review Committee (SRC) comprised of investigators participating in the study made dose escalation decisions based on these criteria.
After completion of the Dose Escalation Phase, the Dose Expansion Phase of the study did not proceed due to the changing landscape in the treatment of HCC. There were no additional safety concerns or safety signals identified in the dose escalation phase of the study.
研究の種類
入学 (実際)
段階
- フェーズ2
- フェーズ 1
連絡先と場所
研究場所
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California
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Los Angeles、California、アメリカ、90095-1752
- UCLA Division of Hematology Oncology
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Florida
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Gainesville、Florida、アメリカ、32610
- University of Florida
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New York
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New York、New York、アメリカ、10016
- NYU Langone Medical Center
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Texas
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Dallas、Texas、アメリカ、75251
- Mary Crowley Cancer Research
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Milan、イタリア、20089
- IRCCS - Istituo Clinico Humanitas - Humanitas Cancer Center
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Pavia、イタリア、27100
- Fondazione IRCCS Policlinico San Matteo
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Roma、イタリア、144
- Istituto Nazionale Tumori Regina Elena
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Barcelona、スペイン、8035
- Hospital Universitario Vall D hebron
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Madrid、スペイン、28034
- Hospital Ramon y Cajal
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Madrid、スペイン、28041
- Hospital 12 de Octubre
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Marseille Cedex 9、フランス、13273
- Institut Paoli Calmettes
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Rennes、フランス、35200
- Centre Eugene Marquis
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Toulouse Cedex、フランス、31059
- Institut Universitaire du Cancer IUCT - Oncopole
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Villejuif CEDEX、フランス、94805
- Institut Gustave Roussy Hematologie
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参加基準
適格基準
就学可能な年齢
健康ボランティアの受け入れ
受講資格のある性別
説明
Inclusion Criteria:
- Subjects must satisfy the following criteria to be enrolled in the study:
- Subject is ≥ 18 years of age at the time of signing the informed consent form (ICF)
- Subject has a confirmed pathologic diagnosis of Hepatocellular carcinoma (HCC) according to the American Association for the Study of Liver Diseases (AASLD) Guidelines.
- Subjects who have progressed after or were intolerant to no more than 2 previous systemic therapies for unresectable HCC, or are naïve to systemic therapy.
- Subject has at least one measurable lesion according to RECIST 1.1.
- Subject has a life expectancy of ≥ 12 weeks
- Subject has an Eastern Cooperative Oncology Group Performance Status (ECOG PS) of 0 or 1
- Subject has adequate hematologic function and adequate hepatic function at screening
Exclusion Criteria:
- The presence of any of the following will exclude a subject from enrollment:
- Subject has received more than 2 previous systemic therapies for Hepatocellular carcinoma (HCC).
- Subject has received previous treatment with any anti-PD-1 (Programmed death 1) or anti-PD-L1 (PD-1 ligand receptor) antibody
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
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実験的：CC-122 with Nivolumab
CC-122 orally 5/7 days with nivolumab Intravenously (IV) 3mg/kg every 2 weeks.
Cohorts of up to 6 subjects per dose level until Recommended Phase 2 dose (RP2D).
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Incidence of Dose Limiting Toxicities (DLTs)
時間枠：28 days
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During dose escalation, the DLT assessment period is defined as Days 1 to 28 of Cycle 1 including the predose assessments specified for Day 1 of Cycle 2. A DLT is defined as any of the following toxicities occurring within the DLT assessment window unless the event can clearly be determined to be unrelated to the drug. |
28 days
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Incidence and Severity of Treatment-Emergent Adverse Events (TEAEs)
時間枠：From first dose up to 28 days (CC-122) or 90 days (nivolumab) post-last dose (up to 2 years)
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During dose escalation, the TEAE phase 1 assessment period is defined as Days 1 to 28 of Cycle 1 including the predose assessments specified for Day 1 of Cycle 2. Number of participants who experienced a TEAE during the course of the study. |
From first dose up to 28 days (CC-122) or 90 days (nivolumab) post-last dose (up to 2 years)
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Objective Response Rate (ORR) by Response Evaluation Criteria in Solid Tumors Version 1.1 (RECIST 1.1)
時間枠：up to 2 years
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ORR is is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR).
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up to 2 years
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二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Disease Control Rate (DCR) by RECIST 1.1
時間枠：up to 2 years
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DCR is is defined as the number and percentage of participants with a best overall response (BOR) of confirmed complete response (CR) or partial response (PR) or stable disease (SD).
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up to 2 years
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Duration of Response (DoR) by RECIST 1.1
時間枠：up to 2 years
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Duration of response is measured from the date the criterion is first met for CR/PR using RECIST 1.1 rules (whichever is first recorded) until the first date when progressive disease using RECIST 1.1 is documented or death occurred.
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up to 2 years
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Progression-Free Survival (PFS) by RECIST 1.1
時間枠：up to 2 years
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Progression-Free Survival (PFS) is defined as the time from the first dose date of study drug until tumor progression or death, whichever occurs first. A subject who has neither progressed nor died or who progresses or dies after an extended lost-to-follow up time (two or more missed assessments) is censored on the date of last adequate tumor assessment. Subjects without valid baseline or post-baseline tumor assessments are censored on their first dose date. Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data. |
up to 2 years
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Overall Survival (OS) by RECIST 1.1
時間枠：up to 2 years
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Overall Survival (OS) is measured as the time from the first dose of study drug to death from any cause. Participants who have no death reported are censored at the last contact date the participant is known to be alive. Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data. |
up to 2 years
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Time to Progression (TTP) by RECIST 1.1
時間枠：up to 2 years
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Time to Progression (TTP) is defined as the time from the first dose date of study drug until tumor progression; TTP does not include death. The censoring rules are the same as PFS except that deaths without progression are censored at last adequate tumor assessment. Median and the 2-sided 95% confidence interval (CI) are based on Kaplan-Meier estimate of progression-free survival and time to progression using both observed and censored data. |
up to 2 years
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Maximum Observed Concentration (Cmax)
時間枠：28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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Area Under the Concentration Time Curve (AUC)
時間枠：28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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Time to Maximum Concentration (Tmax)
時間枠：28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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Terminal Half-life (T-HALF)
時間枠：28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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Apparent Volume of Distribution (Vz/F)
時間枠：28 days
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Blood was collected according to intensive and sparse sampling strategies to estimate the population pharmacokinetic (PK) of CC-122 when administered in combination with nivolumab.
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28 days
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協力者と研究者
スポンサー
捜査官
- スタディディレクター：Akshay Patel、Celgene Corporation
研究記録日
主要日程の研究
研究開始 (実際)
一次修了 (実際)
研究の完了 (実際)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (見積もり)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
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